Current Topics in Experimental Endocrinology (eBook)

Volume 3

V. H. T. James, L Martini (Herausgeber)

eBook Download: PDF | EPUB

2013 | 1. Auflage
232 Seiten
Elsevier Science (Verlag)
978-1-4832-1735-2 (ISBN)

Infos

Current Topics in Experimental Endocrinology, Volume 3 covers the relationship between the endocrine system and some types of tumors. The book discusses the perspectives, pitfalls, and potentials of tissue culture in endocrine research; the tumor types associated with ectopic adrenocorticotropin hormone secretion, particularly nonendocrine tumors; and the hormonal control of breast cancer growth in women and rats. The text also describes the status of steroid receptors in breast tumors; the physiopathological aspects of prolactin secretion in patients with pituitary tumors; and the biochemical endocrinology of prostatic tumors. The ectopic production of human chorionic gonadotropin and its alpha- and beta-subunits is also considered. Endocrinologists, oncologists, chemists, gynecologists, and students taking related courses will find the book invaluable.

Inhalt

Front Cover 1
Current Topics in Experimental Endocrinology 4
Copyright Page 5
Table of Contents 6
LIST OF CONTRIBUTORS 10
PREFACE 12
Chapter 1. Tissue Culture in Endocrine Research: Perspectives, Pitfalls, and Potentials 14
I. Introduction 15
II. Options in Tissue Culture 17
III. Regulation of Functional Activity and Growth in Endocrine Cells in Culture 33
IV. Secondary Applications of Endocrine Cultures 53
V. Discussion 61
Acknowledgments 63
References 63
Chapter 2. Adrenocorticotropin and Related Peptides in Nonendocrine Tumors 70
I. Introduction 71
II. History 71
III. Definition of Ectopic Adrenocorticotropic Hormone (ACTH) Syndrome 72
IV. Evidence for Existence of Ectopic Humoral Syndromes 72
V. Diagnosis of Ectopic ACTH Syndrome 73
VI. Incidence of Ectopic ACTH Syndrome 74
VII. Clinical Features of Ectopic ACTH Syndrome 75
VIII. Characterization of Ectopic ACTH and Related Peptides 77
IX. Tumor Types Associated with Ectopic ACTH Secretion 82
X. ACTH and Related Peptides in Control Tumors 83
XI. Postulated Mechanisms Leading to Ectopic ACTH Secretion 83
XII. Conclusions 84
References 85
Chapter 3. Hormonal Control of Breast Cancer Growth in Women and Rats 88
I. Introduction 88
II. Experimental Mammary Cancer in the Rat 90
III. Antiprolactin and Antiestrogen Drugs in Women with Breast Cancer 95
IV. Discussion 102
References 103
Chapter 4. Steroid Receptors in Breast Tumors—Current Status 
106 
I. Introduction 107
II. Estrogen 108
III. Progesterone 119
IV. Glucocorticoids 128
V. Androgens 130
VI. Conclusions 135
References 136
Chapter 5. Prolactin and Pituitary Tumors 144
I. Introduction 145
II. A Brief Survey of the Regulation of Prolactin Secretion. . 145
III. Pathological Hyperprolactinemic States 150
IV. Plasma Prolactin Levels in Patients with Pituitary Tumors 154
V. Relationships between Prolactin and Other Pituitary Hormones 167
VI. Plasma Prolactin Levels in Patients without Evidence of Pituitary Tumors 173
VII. Is Hyperprolactinemia a Marker of Pituitary Tumors? 174
VIII. Possible Approaches to the Treatment of the Pathological Hyperprolactinemic States 176
References 179
Chapter 6. Biochemical Endocrinology of Prostatic Tumors 186
I. Introduction 186
II. Benign Prostatic Hypertrophy (BPH) 187
III. Prostatic Carcinoma 197
IV. Conclusions 207
References 208
Chapter 7. Ectopic Production of Human Chorionic Gonadotropin and Its a- and ß-Subunits 214
I. Introduction 215
II. Specific Radioimmunoassays for Circulating HCG and Its a-and ß-Subunits 215
III. Serum Circulating Forms of HCG and Its a- and ß-Subunits 216
IV. Levels of HCG and Its a- and ß-Subunits during Normal Pregnancy 218
V. Levels of HCG and Its Subunits in Patients with Trophoblastic Tumors 221
VI. HCG and Its Subunits in Nontrophoblastic Tumors 225
VII. Summary and Conclusions 227
References 228
SUBJECT INDEX 230

Textauszug

Adrenocorticotropin and Related Peptides in Nonendocrine Tumors

W.J. Jeffcoate and Lesley H. Rees,     Department of Chemical Pathology, St. Bartholomew’s Hospital, London, England

Publisher Summary

This chapter focuses on adrenocorticotropin and related peptides in nonendocrine tumors. The ectopic adrenocorticotropic hormone (ACTH) syndrome is usually defined as the secretion of ACTH and/or of closely related peptides, by a tumor comprised of cells that are not normally engaged in their production. It is the syndrome that results from ACTH secretion by a nonpituitary tumor. It has been established beyond doubt that tumors of certain groups of cells frequently synthesize and secrete ACTH, its precursor forms, or its fragments. The synthesis of ACTH in such tumors is common and includes at least 50% of all oat cell carcinomas of the lung. The formation and secretion of ectopic ACTH is probably invariably accompanied by the formation of βn-LPH-related peptides. The chapter discusses the diagnosis, clinical features, and incidence of ectopic ACTH syndrome, characterization of ectopic ACTH and related peptides, tumor types associated with ectopic ACTH secretion, and ACTH and related peptides in control tumors.

I  Introduction

II  History

III  Definition of Ectopic Adrenocorticotropic Hormone (ACTH) Syndrome

IV  Evidence for Existence of Ectopic Humoral Syndromes

V  Diagnosis of Ectopic ACTH Syndrome

VI  Incidence of Ectopic ACTH Syndrome

VII  Clinical Features of Ectopic ACTH Syndrome

A  Pigmentation

B  Hypokalemia

C  Prognosis

VIII  Characterization of Ectopic ACTH and Related Peptides

A  ACTH and Its Fragments

B  Lipotropic Hormone (LPH) and Its Fragments

C  “Big” ACTH and “Big” LPH

D  Corticotropin-Releasing Factor (CRF)-Like Substances

IX  Tumor Types Associated with Ectopic ACTH Secretion

X  ACTH and Related Peptides in Control Tumors

XI  Postulated Mechanisms Leading to Ectopic ACTH Secretion.

XII  Conclusions

References

I Introduction

Initially, an association was noted between certain nonendocrine tumors and the clinical features of Cushing’s syndrome. Later, it was realized that the association arose because such tumors were capable of the biosynthesis and secretion of adrenocorticotropic substances. These substances were thought at first to be identical to pituitary ACTH (αh1-39ACTH), but it is now known that a variety of ACTH-related peptides may be produced, including both larger precursor molecules and ACTH-like fragments. In addition, the ectopic synthesis of ACTH-like peptides appears to be accompanied, invariably, by the synthesis of a second group of peptides, related to β-lipotropin (β-LPH). The first member of this group identified was the 22-amino acid fragment βh-melanocyte-stimulating hormone (MSH),1 and for this reason the term ectopic ACTH/MSH syndrome came into use. We shall refer to the clinical condition simply as the ectopic ACTH syndrome.

II History

Although the classical description of Cushing’s syndrome was not to be made until 1932 (Cushing, 1932), it is possible to identify earlier reports of the condition. One of these was that by Gabcke (1896) whose patient with a nonendocrine tumor, pigmentation, and hypertrophy of the adrenal glands probably represents the first reported case of the ectopic ACTH syndrome. Then Achard and Thiers (1921) described patients with a condition they termed “le diabete des femmes a barbe” and in 1928 Brown found that one of six cases of “diabetes of bearded women” had an oat cell carcinoma of the lung. Such early studies assumed no causal relationship between the tumors and adrenal hyperplasia, merely calling then pluriglandular syndromes (Leyton et al., 1931; Keppler, 1933). Crooke (1946) noted the relationship between Cushing’s syndrome and carcinoma of the pancreas and commented that “basophilism is a disorder usually associated with tumor formation.” Some assumed that Cushing’s syndrome predisposed to cancer. But it was not until 1952 that Thorne first suggested that these tumors secreted an adrenocorticotropic substance, although he concluded that there was no evidence to support the theory. Ten years later this evidence was forthcoming when Christy (1961) described raised adrenal weight-maintaining activity in the plasma of two patients with lung tumors, and Meador and his colleagues (1962) published their elegant study of five patients with nonpituitary tumors and Cushing’s syndrome and later Liddle et al. (1965) coined the phrase “ectopic ACTH.”

In the last 15 years the ectopic ACTH syndrome has been extensively studied and reviewed (Liddle et al., 1969; Ratcliffe et al., 1972; Rees and Ratcliffe, 1974; Rees, 1975, 1977a). With increasing awareness on the part of physicians and with the increasing availability of sensitive immunoassay and bioassay techniques for the measurement of ACTH and related peptides, the diagnosis is made more frequently. For example, there is good evidence that ectopic ACTH secretion occurs in between one-third and half of all patients with oat cell carcinoma of the lung (Gilby et al., 1975) and that most, if not all, the remainder have the potential for ACTH synthesis.

The realization that the ectopic secretion of ACTH is associated with the ectopic elaboration of other related peptides followed, and the presence of a melanocyte-stimulating factor (called β-MSH at the time) was observed in the plasma and tumor extracts of some patients (Island et al., 1965; Shimizu et al., 1965; Abe et al., 1967a). At the same time Abe described the ectopic secretion of α-MSH (Abe et al., 1967b) in association with ACTH, and it has since become apparent that coincident secretion of many different related and nonrelated peptides may occur (Rees and Landon, 1975).

III Definition of Ectopic Adrenocorticotropic Hormone (ACTH) Syndrome

The ectopic ACTH syndrome is usually defined as the secretion of ACTH, and/or of closely related peptides, by a tumor comprised of cells not normally engaged in their production (Liddle et al., 1969; Ellison and Neville, 1973). Although traditional, this definition is far from perfect for it implies that all the normal sites of ACTH secretion are known, which is probably not true (Rees, 1976; Bloomfield et al., 1977). It is better to say simply that it is the syndrome that results from ACTH secretion by a nonpituitary tumor.

IV Evidence for Existence of Ectopic Humoral Syndromes

The coexistence of a tumor and Cushing’s syndrome does not prove that the former is the cause of the latter. To establish that any hormone is secreted ectopically a number of criteria must be satisfied, listed in Table I. This subject has been discussed in detail elsewhere (Omenn, 1970; Rees, 1977a). In the case of ACTH all but the last of these features have been demonstrated.

Table I

Criteria To Be Established To Demonstrate the Ectopic Secretion of Any Hormone

V Diagnosis of Ectopic ACTH Syndrome

This depends initially on clinical suspicion for, if a condition is thought to be rare, it is only rarely diagnosed. The patient may present only one or two of the clinical features listed below and the classical appearance of Cushing’s syndrome may not occur. However, in any patient with a tumor and associated hypokalemia, the diagnosis should be seriously entertained. Similarly, if a patient with clinical or biochemical features of Cushing’s syndrome has either high ACTH and Cortisol levels or hypokalemia, he may well have ectopic ACTH secretion. In such circumstances the tumor may well be occult and occasionally not become clinically obvious until several years after initial presentation (Bagshawe, 1960).

However, in a suspected case of ectopic ACTH secretion it may well be difficult to find definite...

Produkt-Details

• Erscheint lt. Verlag: 22.10.2013
• Sprache: englisch
• Themenwelt: Sachbuch/Ratgeber ► Gesundheit / Leben / Psychologie ► Krankheiten / Heilverfahren
• Themenwelt: Medizin / Pharmazie ► Allgemeines / Lexika
• Themenwelt: Medizin / Pharmazie ► Medizinische Fachgebiete
• ISBN-10: 1-4832-1735-3 / 1483217353
• ISBN-13: 978-1-4832-1735-2 / 9781483217352